| Summary: | Background: Epidemiological evidence supports a strong association between exposure to inhaled toxins and adverse respiratory outcomes such as pneumococcal pneumonia and chronic respiratory conditions such as chronic obstructive pulmonary disorder (COPD). Chronic exposure to airborne particulate matter in occupational settings, such as welding, has been shown to reversibly increase risk of pneumococcal pneumonia. However, biological plausibility of this has not been shown and the molecular mechanisms are unknown. Chronic cigarette smoking causes reduced lung function and increased morbidity in COPD patients. These patients are highly vulnerable to viral and secondary pneumococcal infections. The molecular mechanisms are unclear. Methods: Association between exposure to welding fumes (WF) and susceptibility to pneumococcal infection, rhinoviral infection and rhinoviral+secondary pneumococcal infection was assessed in lower airway and nasal epithelial cells in vitro. The role of the platelet activating factor receptor (PAFR), which is an entry receptor for the pneumococcus, was also assessed. Using two methods of WF exposure, susceptibility to pneumococcal infection following acute and chronic exposure was assessed in mice. Finally, PAFR expression was examined in the lungs of non-smokers, welders, smokers and smokers with COPD. Results: Exposure of alveolar, bronchial and nasal epithelial cells to WF significantly increases pneumococcal invasion of these cells in a PAFR dependent manner. Exposure to WF increases susceptibility to infection by rhinovirus and vulnerability to secondary pneumococcal infections in a PAFR dependent manner. Exposure to WF increases susceptibility of mice to pneumococcal infection and PAFR mRNA expression levels in the lungs. Finally, PAFR mRNA levels are elevated in smokers with COPD compared with non-smokers. PAFR protein expression in the lungs of smokers with COPD is localised to the bronchial epithelium and bronchial glands. 4 Conclusions: PAFR is a potential anti-infective agent in pneumococcal pneumonia caused by exposure to WF and in COPD caused by chronic exposure to smoking.
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